Major Article

Discontinuing contact precautions for multidrug-resistant organisms:A systematic literature review and meta-analysis

Alexandre R. Marra MD, MS a,b,*, Michael B. Edmond MD, MPH, MPA a,c,Marin L. Schweizer PhD d,e, Grace W. Ryan MPH f, Daniel J. Diekema MD, MS a,c,g

a Office of Clinical Quality, Safety and Performance Improvement, University of Iowa Hospitals and Clinics, Iowa City, IAb Division of Medical Practice, Hospital Israelita Albert Einstein, São Paulo, Brazilc Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IAd The Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, IAe Division of General Internal Medicine, Department of Internal Medicine, Carver College of Medicine, Iowa City, IAf Department of Community and Behavioral Health, University of Iowa, College of Public Health, Iowa City, IAg Division of Medical Microbiology, Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA

Key Words:Stopping contact precautionMRSAVREsystematic reviewmeta-analysismultidrug-resistant organisms

Background: Several single-center studies have suggested that eliminating contact precautions (CPs) formethicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) controlin nonoutbreak settings has no impact on infection rates. We performed a systematic literature reviewand meta-analysis on the impact of discontinuing contact precautions in the acute care setting.Methods: We searched PubMed, CINAHL, Cochrane Database of Systematic Reviews, Database of Ab-stracts of Reviews of Effects, and Embase through December 2016 for studies evaluating discontinuationof contact precautions for multidrug-resistant organisms. We used random-effect models to obtain pooledrisk ratio estimates. Heterogeneity was evaluated with I2 estimation and the Cochran Q statistic. Pooledrisk ratios for MRSA and VRE were assessed separately.Results: Fourteen studies met inclusion criteria and were included in the final review. Six studies dis-continued CPs for both MRSA and VRE, 3 for MRSA only, 2 for VRE only, 2 for extended-spectrumβ-lactamase–producing Escherichia coli, and 1 for Clostridium difficile infection. When study results werepooled, there was a trend toward reduction of MRSA infection after discontinuing CPs (pooled risk ratio,0.84; 95% confidence interval, 0.70-1.02; P = .07) and a statistically significant reduction in VRE infection(pooled risk ratio, 0.82; 95% confidence interval, 0.72-0.94; P = .005).Conclusions: Discontinuation of CPs for MRSA and VRE has not been associated with increased infec-tion rates.

© 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by ElsevierInc. All rights reserved.

BACKGROUND

Contact precautions (CPs) were first recommended by the Centersfor Disease Control and Prevention in 1970,1 at a time when therewas minimal surveillance for health care–associated infections (HAIs),few single-bed hospital rooms, very poor compliance with handhygiene, no use of alcohol-based handrubs, no chlorhexidine bathing

to decolonize patients, and no enhanced technology for environ-mental disinfection.2,3 Over the ensuing decades, more knowledgehas been acquired about strategic approaches to infection preven-tion. Despite the widespread use of CPs, there is little evidence tosupport effectiveness in the prevention of methicillin-resistant Staph-ylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE)infections in endemic settings.4,5 In addition, questions have beenraised regarding the impact of CPs on care delivery and patientsafety.6,7

The objective of this study was to perform a systematic reviewof the literature and meta-analysis of studies that described hos-pitals’ experience in discontinuing CPs for multidrug-resistantorganisms, including MRSA, VRE, Clostridium difficile, and extended-spectrum β-lactamase–producing Escherichia coli (ESBL–E coli) in theacute care setting.

* Address correspondence to Alexandre R. Marra, MD, MS, Office of Clinical Quality,Safety and Performance Improvement, University of Iowa Hospitals and Clinics, C51GH, 200 Hawkins Dr, Iowa City, IA 52242.

E-mail address: alexandre-rodriguesmarra@uiowa.edu (A.R. Marra).Funding/support: M.L.S. is funded through a VA Health Services Research and

Development Service (award no. CDA 11-215).Conflicts of interest: None to report.

0196-6553/© 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.https://doi.org/10.1016/j.ajic.2017.08.031

American Journal of Infection Control 46 (2018) 333-40

Contents lists available at ScienceDirect

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journal homepage: www.aj ic journal .org

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http://crossmark.crossref.org/dialog/?doi=10.1016/j.ajic.2017.08.031&domain=pdfmailto:alexandre-rodriguesmarra@uiowa.eduhttps://doi.org/10.1016/j.ajic.2017.08.031https://doi.org/10.1016/j.ajic.2017.08.031http://www.sciencedirect.com/science/journal/01966553http://www.ajicjournal.org

METHODS

Systematic literature review and inclusion and exclusion criteria

This review was conducted according to the Preferred Report-ing Items for Systematic Reviews and Meta-Analyses statement8 andto the Meta-Analysis of Observational Studies in Epidemiology.9 In-stitutional review board approval was not required. Inclusion criteriafor studies in this systematic review were as follows: original re-search articles; published in peer-reviewed, scientific journals;involved human inpatients; conducted in acute care settings thatdiscontinued CPs for MRSA, VRE, C difficile, or ESBL–E coli; and con-trolled trial or quasi-experimental study design. The literature searchwas limited to the last 30 years (June 1985-December 2016) becausethe first reported discontinuation of CPs occurred in the 1990s. Edi-torials, correspondence, commentaries, and outbreak studies wereexcluded. Studies in which discontinuation of CPs was linked di-rectly to MRSA or VRE microbiologic surveillance (ie, stopping CPsbased on negative cultures for individual patients) were also ex-cluded after careful review.

Search strategy

We performed literature searches in PubMed, CINAHL, Co-chrane Database of Systematic Reviews, Cochrane Central Registerof Controlled Trials, Database of Abstracts of Reviews of Effects,Scopus (which includes Embase abstracts), and PsycINFO via PsycNETwith the terms: (1) contact precautions: (“contact precaution” [MeSHTerms] OR “contact precautions” [MeSH Terms] OR “universal pre-caution” [MeSH Terms] OR “universal precautions” [MeSH Terms]OR “isolation precaution”[All Fields] OR “isolation precautions” [AllFields] OR “barrier precaution” [All Fields] OR “barrier precau-tions” [All Fields] OR “contact isolation” [All Fields] OR “contactisolations” [All Fields]; (2) MRSA: (MRSA [MeSH Terms] ORmethicillin-resistant Staphylococcus aureus [MeSH Terms] OR methi-cillin AND resistant AND Staphylococcus aureus [MeSH Terms] ORcross infection AND cross AND infection [MeSH Terms]; (3) VRE:(VRE [MeSH Terms] OR vancomycin-resistant Enterococcus [MeSHTerms] OR vancomycin AND resistant AND Enterococcus [MeSHTerms]); (4) Clostridium difficile (Clostridium difficile [MeSH Terms]OR C. difficile (C. difficile [MeSH Terms] AND infection [MeSH Terms]AND colonization [MeSH Terms]; and (5) Escherichia coli: (Escheri-chia coli [MeSH Terms] OR ESBL [MeSH Terms] OR beta-lactamase[MeSH Terms] AND extended-spectrum beta-lactamase (extended-spectrum beta-lactamase [MeSH Terms] AND infection [MeSHTerms]. We reviewed the reference lists of retrieved articles to iden-tify studies that were not identified from the preliminary literaturesearches.

When searched alone, the term “contact precautions” yielded 434articles, “MRSA” yielded 18,009 articles, “VRE” yielded 2,385 ar-ticles, “Clostridium difficile” yielded 11,622 articles, and “extended-spectrum beta-lactamase producing Escherichia coli” yielded 547articles. After applying exclusion criteria, we reviewed the full ar-ticles for 74 articles, and 14 studies met the inclusion criteria andwere included in the systematic review (Fig 1).

Data abstraction and quality assessment

Titles and abstracts of all articles were screened to assess whetherthey met inclusion criteria. The reviewers (A.R.M. and G.W.R.) ab-stracted data on study design, population and setting, interventionstested, and measurement of discontinuation for CPs. We used thescale used by Aboelela et al.10 and Cohen et al.11 to review publi-cations regarding discontinuation of CPs. This tool has items

regarding sample representativeness, bias and confounding, de-scription of the intervention, outcomes and follow-up, and statisticalanalysis, which are each ranked 1-4, with 4 being the highest quality.Each reviewed article was assessed as to whether it addressed theaforementioned categories in a manner that was completely ade-quate; partially adequate; inadequate, not stated, or impossible totell; or not applicable.10,11 The authors (A.R.M. and G.W.R.) re-viewed all inconsistent assessments, performed component qualityanalysis independently, and determined results by consensus.12 Forquasi-experimental studies we evaluated whether time series anal-ysis was performed, the rationale for why randomization was notused, and other caveats of a quasi-experimental design.13

Statistical analysis

To meta-analyze the extracted data, we calculated the naturallog of the risk ratios and SEMs for MRSA and VRE studies indepen-dently. All the studies in the meta-analysis except Gandra et al14

evaluated infections as the outcome, not colonization. We usedrandom-effect models to obtain pooled risk ratio (pRR) estimates,using Microsoft Excel 2007 (Microsoft, Redmond, WA) and Co-chrane RevMan version 5.2 (The Cochrane Collaboration,Copenhagen, Denmark). Heterogeneity between studies was evalu-ated using the I2 statistic and the Cochran Q statistic. Publicationbias was assessed by visually evaluating the symmetry of a funnelplot.

RESULTS

Characteristics of included studies

Fourteen studies met the inclusion criteria and were includedin the final review (Table 1). All these studies were considered quasi-experimental studies. Twelve studies were nonrandomized quasi-experimental studies comparing infection rates pre- andpostdiscontinuation of CPs.14-25 Ninety-two percent (11/12) of thesestudies compared rates for specific microorganisms (MRSA, VRE, Cdifficile, or ESBL–E coli), and 1 compared device-associated HAI rates.17

One study was a retrospective observational study26 comparing 2academic hospitals (CPs vs non-CPs), and another was a prospec-tive observational study.27

Most of the studies included in our review were conducted inthe United States (10 studies),14-23 2 studies were performed inSwitzerland,24,27 1 was conducted in Canada,25 and 1 was con-ducted in France.26 Most of the studies discontinued CPs in the entirehospital (12 studies),15-19,21,23-27 one study discontinued CPs in a leu-kemia, bone marrow transplant, and lymphoma service of a cancerinstitute,20 and another study was specific to trauma patients at anacademic medical center.22 Many of the studies included in ourreview were conducted at academic medical centers (10studies),15-20,22,24-27 3 studies were performed at community medicalcenters,19,21,23 and 1 was performed at a cancer institute.20

Nine studies discontinued CPs for MRSA,15-19,21-23 8 studies dis-continued CPs for VRE,15-18,20,22,25 2 studies discontinued CPs forESBL–E coli,24,26 and 1 study stopped CPs for C difficile infection27

(except for hypervirulent strains or patients with stool inconti-nence). Among the 9 MRSA studies,15-19,21-23 6 also discontinued CPsfor VRE,15-18,22 and 3 studies stopped CPs only for MRSA.15,21,23 Among8 VRE studies, 6 also discontinued CPs for MRSA,15-18,22 and 2 studiesstopped CPs only for VRE.20,25 The studies included in this reviewthat discontinued CPs for C difficile (1 study)27 and ESBL–E coli (2studies)24,26 stopped CPs only for the mentioned microorganisms,respectively.

The year that the discontinuation of CPs occurred ranged from1993-2015. The longest study time was 10 years,27 and the

334 A.R. Marra et al. / American Journal of Infection Control 46 (2018) 333-40

shortest study duration was 1 year.22 Nine studies reported com-pliance with an alternative intervention, such as hand hygienecompliance interventions, bare-below-the-elbows, or chlorhexidinebathing.15,17-20,24-27

Half of the studies did not perform active microbiologic surveil-lance for MRSA and VRE to determine colonization14,18,21,22,24,26,27

(Table 1). Of the 9 MRSA studies, 7 performed active surveillance(77.8%). Of 8 VRE studies, 5 performed active surveillance (62.5%).Two studies20,25 discontinued VRE microbiologic surveillance in thepostintervention period (discontinuing CPs for VRE). Both of thesestudies measured only infections as the outcome, not coloniza-tion. Two studies performed molecular typing, one by pulsed-field gel electrophoresis24 and another by polymerase chain reactionribotyping for all isolates with a positive result for the presence ofthe binary toxin gene for C difficile to show that the strain sharedidentity with the strain of the index patient.27 In both studies thetransmission rates were similar to those observed when CPs wereused.24,27

Outcomes measures and follow-up

When we considered the assessment quality of the reviewed ar-ticles (Appendix 1), more than half of the studies (9 studies) wereconsidered completely adequate for reporting compliance rates ofinfection prevention process metrics (hand hygiene, environmen-tal cleaning, and chlorhexidine bathing),15,17-19,24-27 and 1 studyreported compliance with bare-below-the-elbows.17 Most of thesestudies (11 studies) had a clearly defined outcome.15-18,20,21,24-27

There were too few studies of C difficile27 and ESBL–E coli24,26 topool results; however, the 2 ESBL–E coli studies were discordant (oneshowing no change; however, no rates per patient days wereshown26); and one showing an increase in infection-colonization rates(0.41 to 1.87 per 1,000 patient days in hospital A and from 0.54 to1.31 per 1,000 patient days at hospital B20). The C difficile study re-vealed a trend toward increased infection rates (from 2.8 per 10,000patient days in 2004 to 4.3 per 10,000 patient days in 2013, P = .013)but a very low rate of transmission.27

-18,009 Articles identified from database search for MRSA

-2,385 Articles identified from database search for VRE

-11,622 Articles identified from database search for C. difficile

-547 Articles identified from database search for ESBL-E.coli

vs. 434 Articles identified from database search for Contact Precautions (CP)

129 Articles identified from database search for MRSA and CP

49 Articles identified from database search for VRE and CP

54 Articles identified from database search for C. diff and CP

5 Articles identified from database search for ESBL-E.coli and CP

163 Articles excluded: review (44); comments (2); editorial (1); describes current practices (47); clinical trials (8); survey (14); outbreak (21); guidelines (3); quality improvement project (1); microbiology method (9); cost-analysis (5); simulation model (4); systematic review/meta-analysis (2); letter (2)

74 Articles identified for full review

6 Articles included for the systematic review of MRSA & VRE and CP

3 Articles included for the systematic review of MRSA and CP

2 Articles included for the systematic review of VRE and CP

2 Articles included in the systematic review of ESBL-E.coli and CP

1 Articles included in the systematic review of C. difficile and CP

60 Articles excluded for not discontinuing CP

Fig 1. Literature search for articles on discontinuing CPs for MRSA, VRE, Clostridium difficile, or ESBL-E coli. CP, contact precautions; ESBL-E coli, extended-spectrum β-lactamase–producing Escherichia coli; MRSA, methicillin-resistant Staphylococcus aureus; VRE, vancomycin-resistant enterococci.

335A.R. Marra et al. / American Journal of Infection Control 46 (2018) 333-40

Table 1Summary of characteristics of studies included in the systematic review

First author,year, location Study design

Study setting(no. of beds)

Studyperiod (y)

Pathogens for whichCPs discontinued

Year CPsdiscontinued

Activemicrobiologicsurveillance

Compliancewith alternative

interventionsto CPs reported Outcome (rates of infection)

Gandra, 2014,14

Worcester, MAQE (pre-post

interventioncomparison)

Entire academicmedical center (781)

2 MRSA, VRE 2010 Yes (MRSA and VRE inadult ICUs and VRE inBMT unit)

No No impact on MRSA or VRE acquisition rates(MRSA: 0.77 to 0.017 per 1,000 patient days;VRE: 1.39 to 0.016 per 1,000 patient days)

Edmond, 2015,17

Richmond, VAQE (pre-post

interventioncomparison)

Entire academicmedical center (865)

2.5 MRSA, VRE 2013 No (except for MRSA inNICU)

Yes No impact on MRSA or VRE device-associatedHAI rates (MRSA: 15 to 12 per 1,000 devicedays; VRE: 22 to 17 per 1,000 device days)

Graman, 2015,16

Rochester, NYQE (pre-post

interventioncomparison)

Entire academicmedical center (800)

2.25 MRSA, VRE 2014 Yes (only forpreoperative MRSAscreening)

No No impact on MRSA HAI rate (MRSA: 3.56 to3.56 per 10,000 patient days; VRE: no rateswere shown)

Rupp, 2017,18

Omaha, NEQE (pre-post

interventioncomparison)

Entire academicmedical center (800)

2 MRSA, VRE 2015 No Yes No impact on MRSA or VRE HAI rates (MRSA:0.55 to 0.48 per 1,000 patient days; VRE: 0.45to 0.32 per 1,000 patient days)

Almyroudis, 2016,20

Buffalo, NYQE (pre-post

interventioncomparison)

Leukemia, BMT andlymphoma service ofa cancer institute(125)

6 VRE 2011 Discontinued VREsurveillance in theposttest

Yes No impact on VRE BSI rate (VRE: 2.32 to 1.87per 1,000 patient days)

Martin, 2016,15 LosAngeles, CA

QE (pre-postinterventioncomparison)

A: academic medicalcenter (540); B:community teachinghospital (265)

2 MRSA, VRE 2014 Yes Yes A: No impact on MRSA or VRE HAI rates; B: Noimpact on MRSA or VRE BSI rates (MRSA:0.40 to 0.32 per 100 admissions; VRE: 0.48 to0.40 per 100 admissions)

Deatherage, 2016,19

Placerville, CAQE (pre-post

interventioncomparison)

Entire communitymedical center (113)

4 MRSA (colonization,not infection)

2014 Yes (MRSA) Yes No impact on MRSA HAI rate (MRSA: 0.152 to0.124 per 1,000 patient days)

Lemieux, 2016,25

Ontario, CanadaQE (pre-post

interventioncomparison)

Four large academichospitals (2,200)

3.5 VRE 2012 Discontinued VREsurveillance in theposttest

Yes No impact on VRE HAI rate (VRE: no rates wereshown, but it was shown the incidence rateratio: 0.59; 95% CI, 0.24-1.47)

Watkins, 2014,22

Austin, TXQE (pre-post

interventioncomparison)

Trauma patients of anacademic medicalcenter (188)

1 MRSA, VRE 2012 No No No impact on MDRO HAI rate (MRSA: 2.05 to2.47 per 1,000 admissions; VRE: no rateswere shown)

Spence, 2012,23

Kalispell, MTQE (pre-post

interventioncomparison)

Entire communitymedical center (285)

4 MRSA 2010 Yes No No impact on MRSA HAI rate (MRSA: 0.049 to0.086 per 1,000 acute care hospital days)

Fazal, 1996,21 SouthBronx, NY

QE (pre-postinterventioncomparison)

Entire communitymedical center (725)

3.6 MRSA 1993 No No No impact on MRSA colonization- infectionrate (MRSA: no rates were shown)

Widmer, 2017,27

Basel, SwitzerlandQE (prospective

observationalstudy)

Entire academicmedical center (735)

10 Clostridium difficile(except hypervirulentstrains, incontinentpatients)

2004 Yes (roommates) Yes Overall increase in C difficile rate, butextremely low transmission demonstratedvia whole genome sequencing (2.8 per10,000 patient days in 2004 to 4.3 per 10,000patient days in 2013)

Tschudin-Sutter,2016,24 Basel,Switzerland

QE (pre-postinterventioncomparison)

A: academic medicalcenter (735); B:academic-affiliatedgeriatric andrehabilitation center(320)

A: 2 B: 1.5 ESBL–E coli 2012 Yes (roommates) Yes No impact on ESBL–E coli HAI- colonizationrates (no rates were shown)

Zahar, 2015,26

Paris, FranceQE (retrospective

study comparing2 hospitals)

Entire academicmedical center (800)

5 ESBL–E coli (except inNICU)

2008 Yes (ICU patients) Yes Increase in ESBL–E coli colonization-infectionrate but no statistical testing performed(0.41 to 1.87 per 1,000 patient days inhospital A; and 0.54 to 1.31 per 1,000 patientdays at hospital B)

BMT, bone marrow transplant; BSI, bloodstream infection; CI, confidence interval; CP, contact precaution; ESBL–E coli, extended-spectrum β-lactamase–producing Escherichia coli; HAI, health care–associated infection; ICU,intensive care unit; MDRO, multidrug-resistant organism; MRSA, methicillin-resistant Staphylococcus aureus; NICU, neonatal intensive care unit; QE, quasi-experimental; VRE, vancomycin-resistant enterococci.

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When the results of the MRSA and VRE studies were pooled,discontinuation of CPs for MRSA was associated with a nonsignifi-cant reduction in MRSA infection rates (pRR, 0.84; 95% confidenceinterval [CI], 0.70-1.02; P = .07).15-19,22,23 Discontinuation of CPs forVRE was associated with a statistically significant reduction in VREinfection rates (pRR, 0.82; 95% CI, 0.72-0.94; P = .005).15,17,18,20,25 Theresults of both meta-analyses for MRSA and for VRE were homo-geneous (MRSA: heterogeneity P = 1.0, I2 = 0%; VRE: heterogeneityP = .91, I2 = 0%) (Figs 2A and 2B). The MRSA study by Fazal et al21

and the VRE study by Watkins et al22 were not included in themeta-analysis because it was not possible to calculate the risk ratiowith the available data. We also reanalyzed the data using onlyMRSA full articles, excluding 2 studies in abstract form (Gramanet al16 and Deatherage19). This resulted in no change in our find-ings (data not shown). There was little evidence of publication biasamong MRSA and VRE studies as shown by the funnel plots inFigures 3A and 3B.

DISCUSSION

This systematic review and meta-analysis found that discon-tinuing CPs for endemic MRSA and VRE across multiple healthcare facilities has not resulted in a detectable increase in MRSA orVRE infection rates. A growing number of U.S. hospitals are rethink-ing CP practices principally for patients colonized or infected with

MRSA and VRE28,29 and focusing resources on horizontal infectioncontrol strategies to prevent multidrug-resistant organisms,2 strat-egies that include hand hygiene, bare-below-the-elbows,chlorhexidine bathing, care bundles, and environmental hygiene.3

Our analysis demonstrated that these hospitals are not seeingimmediate increases in infection rates, or indeed may be seeingreduced infection rates, without the use of gowns and gloves onentering patients’ rooms.29

Different hypotheses could explain our results and should be ex-plored in future studies. The first hypothesis is that CPs are noteffective at preventing endemic MRSA and VRE infections; there-fore, discontinuation of CPs does not change rates of these infections.Studies should explore whether this hypothesized lack of effec-tiveness is because of low health care worker compliance with CPsor low transmission of endemic infections as seen in the includedC difficile study.27 Alternatively, this difference could be explainedby other effective interventions replacing CPs after CP discontinu-ation. One included study that described additional interventionsstated they established 3 horizontal interventions (dailychlorhexidine bathing of all inpatients, a hand hygiene protocol, anda recommendation of a bare-below-the-elbows protocol) prior toCP discontinuation.17 However, most of the included studies wereunclear as to what interventions replaced CPs.

In our systematic literature review, all the included studies(14 studies) were nonrandomized quasi-experimental studies.15-27

A

B

Fig 2. Forest plots of the associations between discontinuing CPs and (A) methicillin-resistant Staphylococcus aureus or (B) vancomycin-resistant enterococci infections. CI,confidence interval; CP, contact precautions; IV, inverse variance weighting; SE, SEM.

337A.R. Marra et al. / American Journal of Infection Control 46 (2018) 333-40

Quasi-experimental studies attempt to demonstrate causalitybetween an intervention and an outcome and encompass a broadrange of nonrandomized intervention studies. These designs are fre-quently used when it is not logistically feasible or ethical to conducta randomized controlled trial.13 In our review, the outcome mea-sures demonstrated no negative impact either for hospital infectionrates, or for infection rates for the specific pathogen studied. Manyhospitals discontinuing CPs for MRSA or VRE continued to performactive surveillance culturing for these pathogens.14,15,17,19,20,23,25 Mi-crobiologic screening in these studies was not used to discontinueCPs but to ensure that discontinuation of CPs was not associatedwith increasing transmission of these pathogens. Another interest-ing point is that hospitals that discontinued CPs for MRSA or VREcontinued to apply CPs for C difficile and multidrug-resistant gram-negative rods.14-18,22

Our results are consistent with previously published con-trolled trials in which expanded use of CPs for carriers of MRSA andVRE was not associated with significantly reduced rates of MRSA

and VRE infections.5,30,31 Huskins et al, in a cluster randomized trialin 18 intensive care units (ICUs), found that universal MRSA and VREscreening (with CPs for carriers) did not reduce MRSA and VRE in-fection or acquisition beyond that of control ICUs.5 This was despitethe use of gloves or CPs for 92% of MRSA- or VRE-colonized ICU days(vs 38% on control ICUs).5 Likewise, Huang et al found that univer-sal use of decolonization strategies (CHG [chlorhexidine gluconatebathing] and mupirocin) was superior to MRSA screening and CPsat reducing MRSA clinical cultures and all-cause bloodstream in-fections in a 74-ICU cluster randomized trial.30 Finally, Derde et al,reporting results from a 13-ICU cluster randomized trial, found noadditional decrease in multidrug-resistant organism acquisition (in-cluding MRSA and VRE) associated with screening and CPs after aninitial hand hygiene and CHG bathing intervention.31

The best current evidence to support use of CPs for multidrug-resistant organism control in the endemic setting is from the Benefitsof Universal Gown and Glove (BUGG) use study, a cluster random-ized trial in 20 ICUs that compared CPs for all patient encounters

A

B

Fig 3. Funnel plots demonstrating the association between discontinuing contact precautions and (A) methicillin-resistant Staphylococcus aureus or (B) vancomycin-resistant enterococci infections. RR, risk ratio; SE, SEM.

338 A.R. Marra et al. / American Journal of Infection Control 46 (2018) 333-40

with standard care.4 The investigators found no difference betweenintervention and control units in the primary outcome of MRSA andVRE acquisition events combined. However, they found that the in-tervention units had a statistically significantly higher reduction inMRSA acquisition events (an incremental reduction of 2.98 eventsper 1,000 patient days).4 The BUGG study intervention (universalCPs) goes well beyond that which we evaluated in this study, butthe results help explain why the clinical impact of CPs use may beso small as to be difficult to detect even in a very large trial (or ameta-analysis). The BUGG study found a decrease of 1 MRSA ac-quisition for every 336 patient days of the universal CPs intervention.Given that there were 4 room entries per hour (96 per day) in theintervention arm, and given current best assumptions regarding thenumber of acquisition events because of transmission and thenumber of acquisitions that result in infection, >500,000 pro-tected (gowned and gloved) encounters are likely to be necessaryto prevent a single MRSA infection.32 Therefore, even if CPs wereeffective in preventing MRSA transmission in the endemic setting,it is unlikely we will see a trial large enough to demonstrate animpact on an infection outcome.

Three recent systematic reviews on the effectiveness of CPs11,29,33

have also concluded there were no high-quality data to support theuse of CPs for endemic MRSA or VRE, and raised concern that theremay be patient harm and unintended consequences.29 Unin-tended consequences associated with CPs have been welldocumented in the literature.6,7,33 These include decreased time spentwith patients, delays in transfer of patients between inpatient units,excess attributable length of stay, increased readmission rates, andpatients’ perception of poor quality of care.33-37 In one study,27 theincidence of C difficile infection increased after discontinuing CPs;however, whole genome sequencing revealed that transmission wasextremely low (n = 2) without CPs.

A limitation of our study was that we included many studiesthat were before-after quasi-experimental studies, which are subjectto multiple biases.13 Quasi-experimental study is the most commonstudy design in the infection prevention literature.29 However,study quality regarding compliance rates, bias and confounding,and failure to adjust for confounders and confirm equivalencybetween pre- and posttest groups is a limitation of this review,and it does not allow us to draw more conclusions from thisevidence regardless of these studies’ findings.9,10 Finally, our meta-analysis was only as valid as the studies that contribute to thepRR. We agree that the results of this meta-analysis should beinterpreted with caution; however, we observe that there were noresults favoring CPs use for MRSA or VRE, and there was no evi-dence of publication bias in our results evaluated by funnel plots,acknowledging that funnel plot analysis is still a subjective analy-sis. Multicenter, carefully designed studies should be performedto evaluate the impact of discontinuation of CPs and determinewhich interventions (eg, chlorhexidine bathing, bare-below-the-elbows, improved hand hygiene compliance) could be used toreplace CPs as an intervention to reduce rates of endemic MRSAand VRE infections.

In conclusion, we found no evidence that discontinuation ofroutine CPs for patients with MRSA or VRE has been associatedwith an increase in MRSA or VRE infection rates in acute care set-tings. These results are limited by the design of the studies includedin our review and meta-analysis, and are not applicable to epidem-ic (eg, outbreak) situations. Nor are there sufficient studies toevaluate the impact of discontinuing CPs for resistant gram-negative pathogens or C difficile. We think discontinuation of CPs(as currently practiced) for MRSA and VRE can be safely accom-plished, particularly in hospitals with a strong horizontal infectionprevention strategy, including high levels of compliance with handhygiene.

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APPENDIX 1. QUALITY ASSESSMENT SCORES FOR THE REVIEWED MANUSCRIPTS*

Qu

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Gan

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Gra

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16

Ru

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Wid

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RepresentativenessStudy population description 4 3 2 2 4 4 2 4 4 3 2 4 4 4Inclusion and exclusion criteria 4 3 2 3 4 4 2 4 3 3 2 4 4 4Location and setting description 4 2 2 2 4 4 2 4 4 3 4 4 4 4

Bias and confoundingStudy population corresponded to larger population in all key factors 1 1 1 1 1 1 1 1 1 1 1 1 1 1Masking 1 1 1 1 1 1 1 1 1 1 1 1 1 1How similar was the assessment of outcomes between groups 4 4 1 4 4 4 1 4 4 1 1 4 4 4Involvement from author 1 1 1 1 1 1 1 1 1 1 1 1 1 1Accounted for confounding interventions 2 2 2 2 3 4 2 4 2 2 2 4 4 4Compliance rates 2 4 2 4 4 4 3 4 2 2 2 4 4 4

Description of interventionReplication possible given descriptions of intervention 4 4 2 4 4 4 2 4 4 3 3 4 4 3

Outcomes and follow-upOutcome assessment procedure clearly defined 4 4 3 4 4 4 2 4 3 4 3 4 4 4Groups equivalent in attrition, LOS, death, or patient days 4 3 2 3 4 3 2 4 2 2 2 4 3 4

Statistical analysisDescription and appropriateness of methods 4 4 2 4 4 4 2 4 4 3 4 4 4 4Tested differences between groups and variability 4 2 2 2 4 4 2 4 4 2 2 4 2 4

1, not applicable; 2, inadequate, not stated; 3, partially adequate; 4, completely adequate; LOS, length of stay.

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Discontinuing contact precautions for multidrug-resistant organisms: A systematic literature review and meta-analysis Background Methods Systematic literature review and inclusion and exclusion criteria Search strategy Data abstraction and quality assessment Statistical analysis

Results Characteristics of included studies Outcomes measures and follow-up

Discussion References